Martha Constantine-Paton studies the formation and modification of synapses -- the interconnections between neurons -- in order to understand how experience shapes the wiring of the brain. By studying individual neurons in the visual system of developing animals, she showed that a class of molecules known as NMDA receptors plays an essential role in setting the strengths of synapses. NMDA receptors are thought to underlie many aspects of learning throughout life, and Constantine-Paton is interested in the role these receptors play in developmental disorders that have their origins in early life.

Wiring the brain through experience

The human brain contains over 100 billion neurons, each connecting to thousands of other neurons in a network of unimaginable complexity. The extraordinary increase in cognitive ability that occurs during childhood is due largely to changes in these interconnections. Synaptic changes are driven by experience, through patterns of electrical activity in the brain that strengthen the desirable connections while weakening or removing those that are unwanted.

Martha Constantine-Paton wants to understand how this process works at the level of individual neurons and their molecular components. By studying the visual system of developing animals, she has shown that a class of molecules known as NMDA receptors plays an essential role in setting the strength of synaptic connections in response to visual experience. Without these NMDA receptors, the visual system fails to undergo the normal tuning process that allows us to perceive the world in sharp detail. Constantine-Paton is now working to understand how exactly NMDA receptors and other associated synaptic molecules control this process.

From synapses to developmental disorders

In addition to affecting development, synaptic plasticity is thought to underlie many forms of learning throughout life. Understanding the relationship between learning and development may help explain why children learn new skills more readily than adults, and why they recover much better than adults from brain damage. It will also have implications for understanding the many developmental disorders that have their origins in early life.

Constantine-Paton is currently focusing on a mouse mutation known as ‘Flailer,' in which the transport of molecules to synaptic sites is disrupted. Flailer mice show a variety of behavioral abnormalities, and many brain regions in these mice lack a form of synaptic plasticity known as long-term depression. Constantine-Paton is using CRISPR genome-editing methods to remove the mutant Flailer protein in different brain regions, thus reversing these synaptic deficits and enabling her to identify the circuits responsible for the abnormal behavioral effects.

Biography:

Constantine-Paton, a founding member of the McGovern Institute, is a professor in the Department of Brain and Cognitive Sciences, and also holds an appointment in the Department of Biology. She moved to MIT in 1999, having previously held professorships at Princeton University and later at Yale University where she was director of the Interdepartmental Neuroscience Program. She has received a lifetime achievement award from the Society for Neuroscience, and in 2013 she was elected to the American Academy of Arts and Sciences.